Non-Cross-Resistant Agents for Ovarian Cancer

Non-Cross-Resistant Agents for Ovarian Cancer

BOCA RATON, Fla--Topotecan (Hycamtin) and other non-cross-resistant
drugs appear to be good salvage therapy for patients with recurrent ovarian
cancer, Robert F. Ozols, PhD, said at the annual meeting of the Network
for Oncology Communication and Research.

He noted that oncologists are "very good at getting people into
a clinical complete remission," using cytoreductive surgery and standard
first-line regimens of cisplatin (Platinol) or carboplatin (Para-platin)
plus paclitaxel (Taxol). "But the problem is that most of these patients
will recur," said Dr. Ozols, senior vice president of medical science,
Fox Chase Cancer Center.

For those who recur with drug-sensitive disease, there is no need to
switch to non-cross-resistant agents, he said. For patients who recur with
drug-resistant or drug-refractory disease, a number of newer non-cross-resistant
drugs are available.

These include the topoisomerase I inhibitor topotecan (Hycamtin), oral
etoposide (VePesid), gemcitabine (Gemzar), vinorelbine (Navelbine), and
liposomal doxorubicin (Doxil), along with two older drugs, hexamethymela-mine
(Hexalen) and ifosfamide (Ifex).

In a European trial, Dr. Ozols said, patients with recurrent ovarian
cancer who did not receive paclitaxel up-front were randomized to receive
topotecan or paclitaxel. The results showed a response rate of 23% for
topotecan versus 14% for paclitaxel, response duration of 32 weeks versus
20 weeks, and time to progression of 23 weeks versus 14 weeks.

"Of course," Dr. Ozols said, "all you can really conclude
from this type of study is that topotecan is an active agent in recurrent
disease." The study is irrelevant to today's practice, he said, since
"everyone starts off with a first-line treatment of paclitaxel."

As a second-line treatment, topotecan is usually given at the FDA-approved
dosing schedule of 1.5 mg/m2 qd × 5 every 3 weeks. The
dose-limiting toxicity in phase I trials was hematologic, primarily neutro-penia.
However, Dr. Ozols said that the hematologic problems are both predictable
and manageable.

"And since there is no evidence that a higher dose equals a higher
response," he said, "you can back off early if there are signs
of hematologic toxicity." He even suggests starting with a lower dose
if patients have had extensive therapy, and decreasing the dose at the
first signs of even mild hematologic toxicity.

The future direction of topotecan use, he said, involves giving it at
different schedules, combining it with other agents, and giving it as part
of initial therapy.

Dr. Ozols also described a Gynecologic Oncology Group trial of oral
etoposide in 70 patients with recurrent ovarian cancer. Platinum-resistant
patients had an overall 27% response rate with oral etoposide and platinum-sensitive
patients had a 34% response rate.

Gemcitabine, which is approved for use in pancreatic cancer, is currently
being studied in Europe where it is showing a 19% response rate in platinum-resistant
tumors. There is also evidence of a possible in vitro synergy between gem-citabine
and cisplatin.

Results are expected soon for studies in recurrent ovarian cancer of
liposomal doxorubicin and the vinca alkaloid vinorelbine, he added.

While there are many trials going on and many agents now available,
there is no drug of choice in second-line treatment, Dr. Ozols said. So
the criteria for selecting second-line therapy lies in three areas--patient
preference, toxicity profile, and oral versus IV.

He recommends selecting a drug and evaluating the patient after two
courses of treatment. "If the drug is not working, then try another
agent," he said. "The worst we can do is administer a drug that
is not effective."

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